MS4A1 encodes CD20, the founding member of the MS4A family of tetraspanning membrane proteins. CD20 is a non-glycosylated, S-palmitoylated four-pass plasma membrane protein with cytoplasmic N and C termini and two short extracellular loops, expressed exclusively on B lymphocytes from the late pre-B stage until terminal differentiation into plasma cells. It resides constitutively in membrane rafts, self-associates (cryo-EM resolves a compact double-barrel dimer; biochemical data suggest higher oligomers), and associates with surface IgM of the B cell antigen receptor (BCR), dissociating upon receptor engagement. CD20 is required for BCR-stimulated store-operated calcium entry and increases transmembrane Ca2+ conductance when expressed ectopically; whether it forms a channel itself or regulates a store-operated channel remains unresolved. CD20 also organizes the nanoscale arrangement of receptors on resting B cells, restraining IgM-BCR/CD19 association and signaling; its ablation in human B cells causes transient activation and loss of the resting state. Loss of CD20 in humans causes common variable immunodeficiency 5, with normal B cell development but impaired T cell-independent antibody responses. CD20 is the target of therapeutic monoclonal antibodies (rituximab, ofatumumab, obinutuzumab) used to deplete B cells in lymphoma and autoimmune disease.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0002115 store-operated calcium entry | IMP PMID:12920111 Store-operated cation entry mediated by CD20 in membrane raf... | ACCEPT | Summary: CD20 is required for B cell receptor-stimulated store-operated calcium entry: siRNA knockdown of CD20 in B cells reduced BCR-stimulated influx, and ectopic CD20 introduced a raft-dependent SOC entry pathway in CHO cells. Reason: Direct loss-of-function (siRNA) evidence in B cells plus gain-of-function in heterologous cells places CD20 as a component of the SOC entry pathway downstream of the BCR. This is the best-supported process role of CD20 and is corroborated by reduced CD19-induced calcium responses in CD20-/- mouse B cells (PMID:14688067). Whether CD20 forms the pore or regulates/organizes an ORAI/STIM-type channel is unresolved, so the process term (not a channel MF) is the appropriate assertion. Supporting Evidence: PMID:12920111 B cell receptor-stimulated influx was significantly reduced by downregulation of CD20 expression using short interfering RNA and also by cholesterol depletion PMID:12920111 This is the first evidence that raft-associated CD20 constitutes a component of a SOC entry pathway activated by the B cell receptor. PMID:14688067 CD19-induced intracellular calcium responses were significantly reduced in CD20(-/-) B cells, with a less dramatic effect on IgM-induced responses. file:human/MS4A1/MS4A1-uniprot.txt Functions as a store-operated calcium (SOC) channel component promoting calcium influx after activation by the B-cell receptor/BCR |
| GO:0005154 epidermal growth factor receptor binding | IEA GO_REF:0000107 | REMOVE | Summary: Electronic transfer (Ensembl Compara) from a rat Ms4a1 ortholog annotation asserting epidermal growth factor receptor binding. Reason: No human or mouse study links CD20 to EGFR, and the two proteins are not co-expressed in a physiological setting: CD20 is B-cell restricted, whereas EGFR is not a B-cell receptor. CD20 interaction data consistently point to the BCR (IgM), MHC class II and itself. The ortholog-projected binding claim is not supported by the biology of the human protein and is not informative about its function. Supporting Evidence: file:human/MS4A1/MS4A1-uniprot.txt Expressed on B-cells. file:human/MS4A1/MS4A1-uniprot.txt Interacts with the heavy and light chains of cell surface IgM, the antigen-binding components of the BCR PMID:18474602 Two major surface-labeled proteins that coprecipitated with CD20 were identified as the heavy and light chains of cell surface IgM, the antigen-binding components of the BCR. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: High-throughput binary interaction with UniProtKB:Q8N6L0 reported in the HI-II-14 proteome-scale yeast two-hybrid map. Reason: Generic protein binding is uninformative about CD20 function. The interaction with UniProtKB:Q8N6L0 comes from a systematic yeast two-hybrid screen without follow-up in B cells; many HuRI partners of CD20 are ER/membrane proteins (e.g. REEP2/REEP4, TMX2, SLC10A1, HSD17B11) consistent with promiscuous membrane-protein pairing in Y2H. Removal does not imply the interaction is false; the functionally informative CD20 interactions (IgM BCR, self-association) are captured by other annotations. Supporting Evidence: PMID:25416956 Here, we describe a systematic map of |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interaction with UniProtKB:A0PK05 reported in the HuRI (HI-III-20) binary yeast two-hybrid reference interactome. Reason: Generic protein binding is uninformative about CD20 function. The interaction with UniProtKB:A0PK05 comes from a systematic yeast two-hybrid screen without follow-up in B cells; many HuRI partners of CD20 are ER/membrane proteins (e.g. REEP2/REEP4, TMX2, SLC10A1, HSD17B11) consistent with promiscuous membrane-protein pairing in Y2H. Removal does not imply the interaction is false; the functionally informative CD20 interactions (IgM BCR, self-association) are captured by other annotations. Supporting Evidence: PMID:32296183 Specifically, yeast two-hybrid (Y2H) represents the only binary PPI assay that can be operated at sufficient throughput to systematically screen the human proteome for binary PPIs. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interaction with UniProtKB:A8MZ59 reported in the HuRI (HI-III-20) binary yeast two-hybrid reference interactome. Reason: Generic protein binding is uninformative about CD20 function. The interaction with UniProtKB:A8MZ59 comes from a systematic yeast two-hybrid screen without follow-up in B cells; many HuRI partners of CD20 are ER/membrane proteins (e.g. REEP2/REEP4, TMX2, SLC10A1, HSD17B11) consistent with promiscuous membrane-protein pairing in Y2H. Removal does not imply the interaction is false; the functionally informative CD20 interactions (IgM BCR, self-association) are captured by other annotations. Supporting Evidence: PMID:32296183 Specifically, yeast two-hybrid (Y2H) represents the only binary PPI assay that can be operated at sufficient throughput to systematically screen the human proteome for binary PPIs. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interaction with UniProtKB:O00590 reported in the HuRI (HI-III-20) binary yeast two-hybrid reference interactome. Reason: Generic protein binding is uninformative about CD20 function. The interaction with UniProtKB:O00590 comes from a systematic yeast two-hybrid screen without follow-up in B cells; many HuRI partners of CD20 are ER/membrane proteins (e.g. REEP2/REEP4, TMX2, SLC10A1, HSD17B11) consistent with promiscuous membrane-protein pairing in Y2H. Removal does not imply the interaction is false; the functionally informative CD20 interactions (IgM BCR, self-association) are captured by other annotations. Supporting Evidence: PMID:32296183 Specifically, yeast two-hybrid (Y2H) represents the only binary PPI assay that can be operated at sufficient throughput to systematically screen the human proteome for binary PPIs. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interaction with UniProtKB:O15529 reported in the HuRI (HI-III-20) binary yeast two-hybrid reference interactome. Reason: Generic protein binding is uninformative about CD20 function. The interaction with UniProtKB:O15529 comes from a systematic yeast two-hybrid screen without follow-up in B cells; many HuRI partners of CD20 are ER/membrane proteins (e.g. REEP2/REEP4, TMX2, SLC10A1, HSD17B11) consistent with promiscuous membrane-protein pairing in Y2H. Removal does not imply the interaction is false; the functionally informative CD20 interactions (IgM BCR, self-association) are captured by other annotations. Supporting Evidence: PMID:32296183 Specifically, yeast two-hybrid (Y2H) represents the only binary PPI assay that can be operated at sufficient throughput to systematically screen the human proteome for binary PPIs. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interaction with UniProtKB:P16871 reported in the HuRI (HI-III-20) binary yeast two-hybrid reference interactome. Reason: Generic protein binding is uninformative about CD20 function. The interaction with UniProtKB:P16871 comes from a systematic yeast two-hybrid screen without follow-up in B cells; many HuRI partners of CD20 are ER/membrane proteins (e.g. REEP2/REEP4, TMX2, SLC10A1, HSD17B11) consistent with promiscuous membrane-protein pairing in Y2H. Removal does not imply the interaction is false; the functionally informative CD20 interactions (IgM BCR, self-association) are captured by other annotations. Supporting Evidence: PMID:32296183 Specifically, yeast two-hybrid (Y2H) represents the only binary PPI assay that can be operated at sufficient throughput to systematically screen the human proteome for binary PPIs. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interaction with UniProtKB:P54219-3 reported in the HuRI (HI-III-20) binary yeast two-hybrid reference interactome. Reason: Generic protein binding is uninformative about CD20 function. The interaction with UniProtKB:P54219-3 comes from a systematic yeast two-hybrid screen without follow-up in B cells; many HuRI partners of CD20 are ER/membrane proteins (e.g. REEP2/REEP4, TMX2, SLC10A1, HSD17B11) consistent with promiscuous membrane-protein pairing in Y2H. Removal does not imply the interaction is false; the functionally informative CD20 interactions (IgM BCR, self-association) are captured by other annotations. Supporting Evidence: PMID:32296183 Specifically, yeast two-hybrid (Y2H) represents the only binary PPI assay that can be operated at sufficient throughput to systematically screen the human proteome for binary PPIs. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interaction with UniProtKB:Q13520 reported in the HuRI (HI-III-20) binary yeast two-hybrid reference interactome. Reason: Generic protein binding is uninformative about CD20 function. The interaction with UniProtKB:Q13520 comes from a systematic yeast two-hybrid screen without follow-up in B cells; many HuRI partners of CD20 are ER/membrane proteins (e.g. REEP2/REEP4, TMX2, SLC10A1, HSD17B11) consistent with promiscuous membrane-protein pairing in Y2H. Removal does not imply the interaction is false; the functionally informative CD20 interactions (IgM BCR, self-association) are captured by other annotations. Supporting Evidence: PMID:32296183 Specifically, yeast two-hybrid (Y2H) represents the only binary PPI assay that can be operated at sufficient throughput to systematically screen the human proteome for binary PPIs. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interaction with UniProtKB:Q14973 reported in the HuRI (HI-III-20) binary yeast two-hybrid reference interactome. Reason: Generic protein binding is uninformative about CD20 function. The interaction with UniProtKB:Q14973 comes from a systematic yeast two-hybrid screen without follow-up in B cells; many HuRI partners of CD20 are ER/membrane proteins (e.g. REEP2/REEP4, TMX2, SLC10A1, HSD17B11) consistent with promiscuous membrane-protein pairing in Y2H. Removal does not imply the interaction is false; the functionally informative CD20 interactions (IgM BCR, self-association) are captured by other annotations. Supporting Evidence: PMID:32296183 Specifically, yeast two-hybrid (Y2H) represents the only binary PPI assay that can be operated at sufficient throughput to systematically screen the human proteome for binary PPIs. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interaction with UniProtKB:Q15546 reported in the HuRI (HI-III-20) binary yeast two-hybrid reference interactome. Reason: Generic protein binding is uninformative about CD20 function. The interaction with UniProtKB:Q15546 comes from a systematic yeast two-hybrid screen without follow-up in B cells; many HuRI partners of CD20 are ER/membrane proteins (e.g. REEP2/REEP4, TMX2, SLC10A1, HSD17B11) consistent with promiscuous membrane-protein pairing in Y2H. Removal does not imply the interaction is false; the functionally informative CD20 interactions (IgM BCR, self-association) are captured by other annotations. Supporting Evidence: PMID:32296183 Specifically, yeast two-hybrid (Y2H) represents the only binary PPI assay that can be operated at sufficient throughput to systematically screen the human proteome for binary PPIs. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interaction with UniProtKB:Q3KNW5 reported in the HuRI (HI-III-20) binary yeast two-hybrid reference interactome. Reason: Generic protein binding is uninformative about CD20 function. The interaction with UniProtKB:Q3KNW5 comes from a systematic yeast two-hybrid screen without follow-up in B cells; many HuRI partners of CD20 are ER/membrane proteins (e.g. REEP2/REEP4, TMX2, SLC10A1, HSD17B11) consistent with promiscuous membrane-protein pairing in Y2H. Removal does not imply the interaction is false; the functionally informative CD20 interactions (IgM BCR, self-association) are captured by other annotations. Supporting Evidence: PMID:32296183 Specifically, yeast two-hybrid (Y2H) represents the only binary PPI assay that can be operated at sufficient throughput to systematically screen the human proteome for binary PPIs. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interaction with UniProtKB:Q5JX71 reported in the HuRI (HI-III-20) binary yeast two-hybrid reference interactome. Reason: Generic protein binding is uninformative about CD20 function. The interaction with UniProtKB:Q5JX71 comes from a systematic yeast two-hybrid screen without follow-up in B cells; many HuRI partners of CD20 are ER/membrane proteins (e.g. REEP2/REEP4, TMX2, SLC10A1, HSD17B11) consistent with promiscuous membrane-protein pairing in Y2H. Removal does not imply the interaction is false; the functionally informative CD20 interactions (IgM BCR, self-association) are captured by other annotations. Supporting Evidence: PMID:32296183 Specifically, yeast two-hybrid (Y2H) represents the only binary PPI assay that can be operated at sufficient throughput to systematically screen the human proteome for binary PPIs. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interaction with UniProtKB:Q5SR56 reported in the HuRI (HI-III-20) binary yeast two-hybrid reference interactome. Reason: Generic protein binding is uninformative about CD20 function. The interaction with UniProtKB:Q5SR56 comes from a systematic yeast two-hybrid screen without follow-up in B cells; many HuRI partners of CD20 are ER/membrane proteins (e.g. REEP2/REEP4, TMX2, SLC10A1, HSD17B11) consistent with promiscuous membrane-protein pairing in Y2H. Removal does not imply the interaction is false; the functionally informative CD20 interactions (IgM BCR, self-association) are captured by other annotations. Supporting Evidence: PMID:32296183 Specifically, yeast two-hybrid (Y2H) represents the only binary PPI assay that can be operated at sufficient throughput to systematically screen the human proteome for binary PPIs. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interaction with UniProtKB:Q5T7V8 reported in the HuRI (HI-III-20) binary yeast two-hybrid reference interactome. Reason: Generic protein binding is uninformative about CD20 function. The interaction with UniProtKB:Q5T7V8 comes from a systematic yeast two-hybrid screen without follow-up in B cells; many HuRI partners of CD20 are ER/membrane proteins (e.g. REEP2/REEP4, TMX2, SLC10A1, HSD17B11) consistent with promiscuous membrane-protein pairing in Y2H. Removal does not imply the interaction is false; the functionally informative CD20 interactions (IgM BCR, self-association) are captured by other annotations. Supporting Evidence: PMID:32296183 Specifically, yeast two-hybrid (Y2H) represents the only binary PPI assay that can be operated at sufficient throughput to systematically screen the human proteome for binary PPIs. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interaction with UniProtKB:Q5TGU0 reported in the HuRI (HI-III-20) binary yeast two-hybrid reference interactome. Reason: Generic protein binding is uninformative about CD20 function. The interaction with UniProtKB:Q5TGU0 comes from a systematic yeast two-hybrid screen without follow-up in B cells; many HuRI partners of CD20 are ER/membrane proteins (e.g. REEP2/REEP4, TMX2, SLC10A1, HSD17B11) consistent with promiscuous membrane-protein pairing in Y2H. Removal does not imply the interaction is false; the functionally informative CD20 interactions (IgM BCR, self-association) are captured by other annotations. Supporting Evidence: PMID:32296183 Specifically, yeast two-hybrid (Y2H) represents the only binary PPI assay that can be operated at sufficient throughput to systematically screen the human proteome for binary PPIs. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interaction with UniProtKB:Q6ZMZ0 reported in the HuRI (HI-III-20) binary yeast two-hybrid reference interactome. Reason: Generic protein binding is uninformative about CD20 function. The interaction with UniProtKB:Q6ZMZ0 comes from a systematic yeast two-hybrid screen without follow-up in B cells; many HuRI partners of CD20 are ER/membrane proteins (e.g. REEP2/REEP4, TMX2, SLC10A1, HSD17B11) consistent with promiscuous membrane-protein pairing in Y2H. Removal does not imply the interaction is false; the functionally informative CD20 interactions (IgM BCR, self-association) are captured by other annotations. Supporting Evidence: PMID:32296183 Specifically, yeast two-hybrid (Y2H) represents the only binary PPI assay that can be operated at sufficient throughput to systematically screen the human proteome for binary PPIs. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interaction with UniProtKB:Q6ZT21 reported in the HuRI (HI-III-20) binary yeast two-hybrid reference interactome. Reason: Generic protein binding is uninformative about CD20 function. The interaction with UniProtKB:Q6ZT21 comes from a systematic yeast two-hybrid screen without follow-up in B cells; many HuRI partners of CD20 are ER/membrane proteins (e.g. REEP2/REEP4, TMX2, SLC10A1, HSD17B11) consistent with promiscuous membrane-protein pairing in Y2H. Removal does not imply the interaction is false; the functionally informative CD20 interactions (IgM BCR, self-association) are captured by other annotations. Supporting Evidence: PMID:32296183 Specifically, yeast two-hybrid (Y2H) represents the only binary PPI assay that can be operated at sufficient throughput to systematically screen the human proteome for binary PPIs. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interaction with UniProtKB:Q7Z5P4 reported in the HuRI (HI-III-20) binary yeast two-hybrid reference interactome. Reason: Generic protein binding is uninformative about CD20 function. The interaction with UniProtKB:Q7Z5P4 comes from a systematic yeast two-hybrid screen without follow-up in B cells; many HuRI partners of CD20 are ER/membrane proteins (e.g. REEP2/REEP4, TMX2, SLC10A1, HSD17B11) consistent with promiscuous membrane-protein pairing in Y2H. Removal does not imply the interaction is false; the functionally informative CD20 interactions (IgM BCR, self-association) are captured by other annotations. Supporting Evidence: PMID:32296183 Specifically, yeast two-hybrid (Y2H) represents the only binary PPI assay that can be operated at sufficient throughput to systematically screen the human proteome for binary PPIs. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interaction with UniProtKB:Q86T13 reported in the HuRI (HI-III-20) binary yeast two-hybrid reference interactome. Reason: Generic protein binding is uninformative about CD20 function. The interaction with UniProtKB:Q86T13 comes from a systematic yeast two-hybrid screen without follow-up in B cells; many HuRI partners of CD20 are ER/membrane proteins (e.g. REEP2/REEP4, TMX2, SLC10A1, HSD17B11) consistent with promiscuous membrane-protein pairing in Y2H. Removal does not imply the interaction is false; the functionally informative CD20 interactions (IgM BCR, self-association) are captured by other annotations. Supporting Evidence: PMID:32296183 Specifically, yeast two-hybrid (Y2H) represents the only binary PPI assay that can be operated at sufficient throughput to systematically screen the human proteome for binary PPIs. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interaction with UniProtKB:Q8NBQ5 reported in the HuRI (HI-III-20) binary yeast two-hybrid reference interactome. Reason: Generic protein binding is uninformative about CD20 function. The interaction with UniProtKB:Q8NBQ5 comes from a systematic yeast two-hybrid screen without follow-up in B cells; many HuRI partners of CD20 are ER/membrane proteins (e.g. REEP2/REEP4, TMX2, SLC10A1, HSD17B11) consistent with promiscuous membrane-protein pairing in Y2H. Removal does not imply the interaction is false; the functionally informative CD20 interactions (IgM BCR, self-association) are captured by other annotations. Supporting Evidence: PMID:32296183 Specifically, yeast two-hybrid (Y2H) represents the only binary PPI assay that can be operated at sufficient throughput to systematically screen the human proteome for binary PPIs. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interaction with UniProtKB:Q8WY91 reported in the HuRI (HI-III-20) binary yeast two-hybrid reference interactome. Reason: Generic protein binding is uninformative about CD20 function. The interaction with UniProtKB:Q8WY91 comes from a systematic yeast two-hybrid screen without follow-up in B cells; many HuRI partners of CD20 are ER/membrane proteins (e.g. REEP2/REEP4, TMX2, SLC10A1, HSD17B11) consistent with promiscuous membrane-protein pairing in Y2H. Removal does not imply the interaction is false; the functionally informative CD20 interactions (IgM BCR, self-association) are captured by other annotations. Supporting Evidence: PMID:32296183 Specifically, yeast two-hybrid (Y2H) represents the only binary PPI assay that can be operated at sufficient throughput to systematically screen the human proteome for binary PPIs. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interaction with UniProtKB:Q96BA8 reported in the HuRI (HI-III-20) binary yeast two-hybrid reference interactome. Reason: Generic protein binding is uninformative about CD20 function. The interaction with UniProtKB:Q96BA8 comes from a systematic yeast two-hybrid screen without follow-up in B cells; many HuRI partners of CD20 are ER/membrane proteins (e.g. REEP2/REEP4, TMX2, SLC10A1, HSD17B11) consistent with promiscuous membrane-protein pairing in Y2H. Removal does not imply the interaction is false; the functionally informative CD20 interactions (IgM BCR, self-association) are captured by other annotations. Supporting Evidence: PMID:32296183 Specifically, yeast two-hybrid (Y2H) represents the only binary PPI assay that can be operated at sufficient throughput to systematically screen the human proteome for binary PPIs. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interaction with UniProtKB:Q96P31-6 reported in the HuRI (HI-III-20) binary yeast two-hybrid reference interactome. Reason: Generic protein binding is uninformative about CD20 function. The interaction with UniProtKB:Q96P31-6 comes from a systematic yeast two-hybrid screen without follow-up in B cells; many HuRI partners of CD20 are ER/membrane proteins (e.g. REEP2/REEP4, TMX2, SLC10A1, HSD17B11) consistent with promiscuous membrane-protein pairing in Y2H. Removal does not imply the interaction is false; the functionally informative CD20 interactions (IgM BCR, self-association) are captured by other annotations. Supporting Evidence: PMID:32296183 Specifically, yeast two-hybrid (Y2H) represents the only binary PPI assay that can be operated at sufficient throughput to systematically screen the human proteome for binary PPIs. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interaction with UniProtKB:Q99942 reported in the HuRI (HI-III-20) binary yeast two-hybrid reference interactome. Reason: Generic protein binding is uninformative about CD20 function. The interaction with UniProtKB:Q99942 comes from a systematic yeast two-hybrid screen without follow-up in B cells; many HuRI partners of CD20 are ER/membrane proteins (e.g. REEP2/REEP4, TMX2, SLC10A1, HSD17B11) consistent with promiscuous membrane-protein pairing in Y2H. Removal does not imply the interaction is false; the functionally informative CD20 interactions (IgM BCR, self-association) are captured by other annotations. Supporting Evidence: PMID:32296183 Specifically, yeast two-hybrid (Y2H) represents the only binary PPI assay that can be operated at sufficient throughput to systematically screen the human proteome for binary PPIs. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interaction with UniProtKB:Q9BRK0 reported in the HuRI (HI-III-20) binary yeast two-hybrid reference interactome. Reason: Generic protein binding is uninformative about CD20 function. The interaction with UniProtKB:Q9BRK0 comes from a systematic yeast two-hybrid screen without follow-up in B cells; many HuRI partners of CD20 are ER/membrane proteins (e.g. REEP2/REEP4, TMX2, SLC10A1, HSD17B11) consistent with promiscuous membrane-protein pairing in Y2H. Removal does not imply the interaction is false; the functionally informative CD20 interactions (IgM BCR, self-association) are captured by other annotations. Supporting Evidence: PMID:32296183 Specifically, yeast two-hybrid (Y2H) represents the only binary PPI assay that can be operated at sufficient throughput to systematically screen the human proteome for binary PPIs. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interaction with UniProtKB:Q9H2K0 reported in the HuRI (HI-III-20) binary yeast two-hybrid reference interactome. Reason: Generic protein binding is uninformative about CD20 function. The interaction with UniProtKB:Q9H2K0 comes from a systematic yeast two-hybrid screen without follow-up in B cells; many HuRI partners of CD20 are ER/membrane proteins (e.g. REEP2/REEP4, TMX2, SLC10A1, HSD17B11) consistent with promiscuous membrane-protein pairing in Y2H. Removal does not imply the interaction is false; the functionally informative CD20 interactions (IgM BCR, self-association) are captured by other annotations. Supporting Evidence: PMID:32296183 Specifically, yeast two-hybrid (Y2H) represents the only binary PPI assay that can be operated at sufficient throughput to systematically screen the human proteome for binary PPIs. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interaction with UniProtKB:Q9H6H4 reported in the HuRI (HI-III-20) binary yeast two-hybrid reference interactome. Reason: Generic protein binding is uninformative about CD20 function. The interaction with UniProtKB:Q9H6H4 comes from a systematic yeast two-hybrid screen without follow-up in B cells; many HuRI partners of CD20 are ER/membrane proteins (e.g. REEP2/REEP4, TMX2, SLC10A1, HSD17B11) consistent with promiscuous membrane-protein pairing in Y2H. Removal does not imply the interaction is false; the functionally informative CD20 interactions (IgM BCR, self-association) are captured by other annotations. Supporting Evidence: PMID:32296183 Specifically, yeast two-hybrid (Y2H) represents the only binary PPI assay that can be operated at sufficient throughput to systematically screen the human proteome for binary PPIs. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interaction with UniProtKB:Q9HA82 reported in the HuRI (HI-III-20) binary yeast two-hybrid reference interactome. Reason: Generic protein binding is uninformative about CD20 function. The interaction with UniProtKB:Q9HA82 comes from a systematic yeast two-hybrid screen without follow-up in B cells; many HuRI partners of CD20 are ER/membrane proteins (e.g. REEP2/REEP4, TMX2, SLC10A1, HSD17B11) consistent with promiscuous membrane-protein pairing in Y2H. Removal does not imply the interaction is false; the functionally informative CD20 interactions (IgM BCR, self-association) are captured by other annotations. Supporting Evidence: PMID:32296183 Specifically, yeast two-hybrid (Y2H) represents the only binary PPI assay that can be operated at sufficient throughput to systematically screen the human proteome for binary PPIs. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interaction with UniProtKB:Q9NQQ7-3 reported in the HuRI (HI-III-20) binary yeast two-hybrid reference interactome. Reason: Generic protein binding is uninformative about CD20 function. The interaction with UniProtKB:Q9NQQ7-3 comes from a systematic yeast two-hybrid screen without follow-up in B cells; many HuRI partners of CD20 are ER/membrane proteins (e.g. REEP2/REEP4, TMX2, SLC10A1, HSD17B11) consistent with promiscuous membrane-protein pairing in Y2H. Removal does not imply the interaction is false; the functionally informative CD20 interactions (IgM BCR, self-association) are captured by other annotations. Supporting Evidence: PMID:32296183 Specifically, yeast two-hybrid (Y2H) represents the only binary PPI assay that can be operated at sufficient throughput to systematically screen the human proteome for binary PPIs. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interaction with UniProtKB:Q9Y320 reported in the HuRI (HI-III-20) binary yeast two-hybrid reference interactome. Reason: Generic protein binding is uninformative about CD20 function. The interaction with UniProtKB:Q9Y320 comes from a systematic yeast two-hybrid screen without follow-up in B cells; many HuRI partners of CD20 are ER/membrane proteins (e.g. REEP2/REEP4, TMX2, SLC10A1, HSD17B11) consistent with promiscuous membrane-protein pairing in Y2H. Removal does not imply the interaction is false; the functionally informative CD20 interactions (IgM BCR, self-association) are captured by other annotations. Supporting Evidence: PMID:32296183 Specifically, yeast two-hybrid (Y2H) represents the only binary PPI assay that can be operated at sufficient throughput to systematically screen the human proteome for binary PPIs. |
| GO:0005576 extracellular region | HDA PMID:22664934 Comparison of tear protein levels in breast cancer patients ... | MARK AS OVER ANNOTATED | Summary: Detected by mass spectrometry in human tear fluid proteomics (breast cancer vs control). Reason: CD20 is a four-pass integral plasma membrane protein lacking a signal sequence, with no soluble or secreted form described. Detection in tear fluid most plausibly reflects shed cells or membrane vesicles rather than a bona fide extracellular localization of the protein. CD20 is not mentioned in the paper body text (supplementary table only). Supporting Evidence: PMID:22664934 Over 150 proteins in the tear fluid of CTRL and CA were identified. PMID:2448768 apparently lacks a signal sequence and contains three extensive hydrophobic regions PMID:22615937 CD20 is a non-glycosylated four-pass transmembrane protein with a large extracellular loop located between the third and fourth transmembrane segments |
| GO:0005886 plasma membrane | EXP PMID:12920111 Store-operated cation entry mediated by CD20 in membrane raf... | ACCEPT | Summary: Plasma membrane localization of CD20 in raft fractions, from the SOC entry study in B cells and transfected CHO cells. Reason: CD20 is a well-established cell surface (plasma membrane) tetraspan protein; this is its core location. Supporting Evidence: PMID:12920111 This is the first evidence that raft-associated CD20 constitutes a component of a SOC entry pathway activated by the B cell receptor. file:human/MS4A1/MS4A1-uniprot.txt Cell membrane {ECO:0000269|PubMed:12920111, |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference of plasma membrane localization for the MS4A family node. Reason: Consistent with extensive experimental evidence that CD20 and other MS4A members are plasma membrane tetraspanning proteins. Supporting Evidence: PMID:7684739 each CD20 monomer possesses four membrane spanning domains, and both the amino and carboxy termini reside within the cytoplasm PMID:23874341 GFP-MS4A4A and GFP-MS4A8B, like GFP-CD20, appeared to be expressed at the plasma membrane |
| GO:0005886 plasma membrane | IDA GO_REF:0000052 | ACCEPT | Summary: Plasma membrane localization from immunofluorescence (Human Protein Atlas-style curation). Reason: Consistent with all localization evidence for CD20. Supporting Evidence: PMID:23874341 GFP-MS4A4A and GFP-MS4A8B, like GFP-CD20, appeared to be expressed at the plasma membrane file:human/MS4A1/MS4A1-uniprot.txt Cell membrane {ECO:0000269|PubMed:12920111, |
| GO:0005886 plasma membrane | IDA PMID:23874341 Expression of MS4A and TMEM176 Genes in Human B Lymphocytes. | ACCEPT | Summary: GFP-CD20 expressed in BJAB B cells localizes to the plasma membrane by fluorescence microscopy. Reason: Direct imaging evidence; plasma membrane is the core location of CD20. Supporting Evidence: PMID:23874341 GFP-MS4A4A and GFP-MS4A8B, like GFP-CD20, appeared to be expressed at the plasma membrane |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular location mapping (Cell membrane) to plasma membrane. Reason: Correct mapping, supported experimentally. Supporting Evidence: file:human/MS4A1/MS4A1-uniprot.txt Cell membrane {ECO:0000269|PubMed:12920111, PMID:7684739 each CD20 monomer possesses four membrane spanning domains, and both the amino and carboxy termini reside within the cytoplasm |
| GO:0005886 plasma membrane | NAS PMID:2448768 Isolation and structure of a cDNA encoding the B1 (CD20) cel... | ACCEPT | Summary: Traceable author statement from the original CD20 cDNA cloning paper describing B1 (CD20) as a cell-surface phosphoprotein. Reason: Correct and consistent with later experimental evidence. Supporting Evidence: PMID:2448768 The B1 (CD20) molecule is a Mr 33,000 phosphoprotein on the surface of human B lymphocytes that may serve a central role in the humoral immune response by regulating B-cell proliferation and differentiation. |
| GO:0006959 humoral immune response | NAS PMID:2448768 Isolation and structure of a cDNA encoding the B1 (CD20) cel... | KEEP AS NON CORE | Summary: Author statement from the CD20 cloning paper that B1/CD20 may serve a central role in the humoral immune response. Reason: The speculative 1988 statement has since been substantiated: CD20-deficient patients (CVID5) and CD20-/- mice have impaired T cell-independent antibody responses. However the term is broad and CD20 acts upstream via BCR-coupled calcium signaling; the more specific B cell receptor signaling and SOC entry annotations capture its core contribution. Supporting Evidence: PMID:2448768 The B1 (CD20) molecule is a Mr 33,000 phosphoprotein on the surface of human B lymphocytes that may serve a central role in the humoral immune response by regulating B-cell proliferation and differentiation. PMID:20038800 antibody formation, particularly after vaccination with TI antigens, was strongly impaired in the patient. PMID:20038800 CD20 has a central role in the generation of T cell-independent (TI) antibody responses. |
| GO:0007166 cell surface receptor signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference that MS4A family members act in cell surface receptor signaling pathways. Reason: CD20 participates in signaling downstream of the B cell receptor (a cell surface receptor) and is physically associated with the BCR, so the general IBA term is correct; the more specific GO:0050853 B cell receptor signaling pathway is separately annotated by IDA. Supporting Evidence: PMID:18474602 These data provide new evidence of the involvement of CD20 in signaling downstream of the BCR PMID:18474602 Two major surface-labeled proteins that coprecipitated with CD20 were identified as the heavy and light chains of cell surface IgM, the antigen-binding components of the BCR. |
| GO:0009897 external side of plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference that MS4A members are on the external side of the plasma membrane. Reason: CD20 is a cell-surface antigen whose extracellular loops are exposed and bound by therapeutic antibodies; appropriate localization term for a surface antigen. Supporting Evidence: PMID:22615937 CD20 is a non-glycosylated four-pass transmembrane protein with a large extracellular loop located between the third and fourth transmembrane segments PMID:32792392 Here we present 3.7- to 4.7-angstrom cryo-electron microscopy structures of full-length CD20 in complexes with prototypical type I rituximab and ofatumumab and type II obinutuzumab. |
| GO:0009897 external side of plasma membrane | IEA GO_REF:0000107 | ACCEPT | Summary: Electronic transfer from mouse orthologs of an external side of plasma membrane annotation. Reason: Consistent with the surface exposure of the CD20 extracellular loops recognized by anti-CD20 antibodies. Supporting Evidence: PMID:22615937 CD20 is a non-glycosylated four-pass transmembrane protein with a large extracellular loop located between the third and fourth transmembrane segments PMID:3925015 The B1 molecule is a 32,000 m.w. phosphorylated cell surface protein expressed exclusively by B cells from the mid pre-B until the plasma cell stage of differentiation. |
| GO:0009986 cell surface | IDA PMID:3925015 The B cell surface molecule B1 is functionally linked with B... | ACCEPT | Summary: B1/CD20 detected on the B cell surface with monoclonal antibodies. Reason: CD20 is a classic B cell surface antigen; correct location. Supporting Evidence: PMID:3925015 The B1 molecule is a 32,000 m.w. phosphorylated cell surface protein expressed exclusively by B cells from the mid pre-B until the plasma cell stage of differentiation. |
| GO:0016020 membrane | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO mapping from the CD20-like/MS4A transmembrane domain family to membrane. Reason: Correct but general; plasma membrane is the more specific location and is separately annotated. Supporting Evidence: PMID:7684739 each CD20 monomer possesses four membrane spanning domains, and both the amino and carboxy termini reside within the cytoplasm |
| GO:0019865 immunoglobulin binding | IDA PMID:18474602 CD20 homo-oligomers physically associate with the B cell ant... | MODIFY | Summary: CD20 co-precipitated with the heavy and light chains of cell surface IgM, the antigen-binding component of the B cell receptor. Reason: The evidence specifically identifies IgM (surface IgM BCR) as the CD20-associated immunoglobulin; the more specific child term IgM binding better represents the finding. Note the association was shown by co-precipitation from B cells and may be indirect within the BCR complex; it dissociates upon BCR engagement. Proposed replacements: IgM binding Supporting Evidence: PMID:18474602 Two major surface-labeled proteins that coprecipitated with CD20 were identified as the heavy and light chains of cell surface IgM, the antigen-binding components of the BCR. file:human/MS4A1/MS4A1-uniprot.txt Interacts with the heavy and light chains of cell surface IgM, the antigen-binding components of the BCR |
| GO:0023026 MHC class II protein complex binding | HDA PMID:20458337 MHC class II-associated proteins in B-cell exosomes and pote... | KEEP AS NON CORE | Summary: CD20 was among a small set of proteins specifically co-immunoprecipitated with MHC class II from B-cell exosomes by quantitative mass spectrometry. Reason: Association of CD20 with MHC class II in B cell membranes/exosomes is reproducible but its functional significance is unknown; it is likely part of tetraspanin/raft co-clustering rather than a defining activity of CD20. Supporting Evidence: PMID:20458337 Using quantitative MS, we then identified a small subset of proteins that were specifically co-immunoprecipitated with MHC II from detergent-solubilized exosomes. PMID:20458337 These include HSC71, HSP90, 14-3-3Ι, CD20 and pyruvate kinase type M2 (PKM2) |
| GO:0030183 B cell differentiation | IDA PMID:3925015 The B cell surface molecule B1 is functionally linked with B... | KEEP AS NON CORE | Summary: Anti-B1 (CD20) monoclonal antibodies inhibited immunoglobulin secretion in pokeweed mitogen-stimulated B cell cultures. Reason: The evidence is antibody-ligation perturbation rather than loss of function. Genetic loss of CD20 in humans and mice leaves B cell development largely normal, but antibody formation (plasma cell output) after T-independent immunization is impaired, so a contribution to terminal B cell differentiation is plausible but indirect, downstream of BCR calcium signaling. Retained as non-core; defer to curator on the IDA. Supporting Evidence: PMID:3925015 anti-B1 antibody inhibited immunoglobulin secretion in pokeweed mitogen assays PMID:3925015 These results suggest that the B1 molecule may serve a central role in the regulation of B cell activation and differentiation. PMID:20038800 although antigen-independent B cells developed normally in the absence of CD20 expression PMID:14688067 B cell development, tissue localization, signal transduction, proliferation, T cell-dependent antibody responses and affinity maturation were normal in CD20(-/-) mice. |
| GO:0042100 B cell proliferation | NAS PMID:2448768 Isolation and structure of a cDNA encoding the B1 (CD20) cel... | MARK AS OVER ANNOTATED | Summary: Author statement from the cloning paper that CD20 may regulate B-cell proliferation. Reason: Based on effects of anti-CD20 antibodies on proliferation. CD20-/- mouse B cells proliferate normally, and the antibody effects reflect CD20 ligation rather than a demonstrated role of CD20 itself in executing proliferation. Supporting Evidence: PMID:2448768 The B1 (CD20) molecule is a Mr 33,000 phosphoprotein on the surface of human B lymphocytes that may serve a central role in the humoral immune response by regulating B-cell proliferation and differentiation. PMID:14688067 B cell development, tissue localization, signal transduction, proliferation, T cell-dependent antibody responses and affinity maturation were normal in CD20(-/-) mice. PMID:3925015 The anti-B1 antibodies at concentrations ranging from 0.1 to 100 micrograms/ml significantly inhibited B cell proliferation induced by anti-mu antibodies |
| GO:0042113 B cell activation | IDA PMID:3925015 The B cell surface molecule B1 is functionally linked with B... | ACCEPT | Summary: Anti-B1 antibodies inhibited B cell activation/proliferation induced by anti-mu, SAC, activated T cells and EBV, when present at the start of culture. Reason: CD20 contributes to the early B cell activation response through its role in BCR-coupled calcium entry (PMID:12920111, PMID:18474602). The original evidence is antibody perturbation, but the broad process is consistent with the integrated evidence; accepted, with BCR signaling and SOC entry as the specific mechanism. Supporting Evidence: PMID:3925015 The anti-B1 antibodies at concentrations ranging from 0.1 to 100 micrograms/ml significantly inhibited B cell proliferation induced by anti-mu antibodies PMID:3925015 These results suggest that the B1 molecule may serve a central role in the regulation of B cell activation and differentiation. PMID:12920111 B cell receptor-stimulated influx was significantly reduced by downregulation of CD20 expression using short interfering RNA and also by cholesterol depletion |
| GO:0042802 identical protein binding | IPI PMID:32792392 Binding mechanisms of therapeutic antibodies to human CD20. | KEEP AS NON CORE | Summary: Cryo-EM structures show CD20 assembling as a homodimer in complex with therapeutic antibodies. Reason: Self-association of CD20 is well supported (cryo-EM double-barrel dimer; co-IP homo-oligomers). Homo-oligomerization is structurally important but is not itself the physiological function of CD20. Supporting Evidence: PMID:32792392 Here we present 3.7- to 4.7-angstrom cryo-electron microscopy structures of full-length CD20 in complexes with prototypical type I rituximab and ofatumumab and type II obinutuzumab. PMID:32079680 revealing CD20 as a compact double-barrel dimer bound by two RTX antigen-binding fragments (Fabs) PMID:18474602 we provide here direct evidence of CD20 homo-oligomerization into tetramers |
| GO:0044853 plasma membrane raft | IDA PMID:12920111 Store-operated cation entry mediated by CD20 in membrane raf... | ACCEPT | Summary: CD20 is constitutively associated with membrane rafts, and raft localization is required for CD20-mediated SOC entry. Reason: Direct biochemical evidence; raft association is functionally linked to its calcium entry role. Supporting Evidence: PMID:12920111 The activity of this SOC pathway was abolished by deletion of a cytoplasmic sequence in CD20 essential for its efficient raft localization. file:human/MS4A1/MS4A1-uniprot.txt Constitutively associated with membrane rafts. |
| GO:0050853 B cell receptor signaling pathway | IDA PMID:18474602 CD20 homo-oligomers physically associate with the B cell ant... | ACCEPT | Summary: CD20 homo-oligomers associate with surface IgM of the BCR, dissociate after BCR engagement, and transiently recruit phosphoproteins and calmodulin-binding proteins. Reason: Together with the siRNA evidence that CD20 is needed for BCR-stimulated calcium influx (PMID:12920111), this places CD20 within the BCR signaling pathway (calcium-entry branch). Core process. CRISPR ablation and rescue in human B cells (PMID:33563755) further show CD20 organizes BCR nanodomains and restrains IgM-BCR/CD19 signaling in resting cells, so its role in the pathway is regulatory in both directions depending on activation state; the process term remains appropriate. Supporting Evidence: PMID:18474602 These data provide new evidence of the involvement of CD20 in signaling downstream of the BCR PMID:18474602 Two major surface-labeled proteins that coprecipitated with CD20 were identified as the heavy and light chains of cell surface IgM, the antigen-binding components of the BCR. PMID:12920111 B cell receptor-stimulated influx was significantly reduced by downregulation of CD20 expression using short interfering RNA and also by cholesterol depletion PMID:33563755 In the present study, we show that CD20 controls the proper nanoscale receptor organization on resting B cells and prevents uncontrolled IgM-BCR/CD19 signaling. file:human/MS4A1/MS4A1-deep-research-falcon.md These perturbation-and-rescue results support a *gatekeeper* role |
| GO:0051262 protein tetramerization | IDA PMID:18474602 CD20 homo-oligomers physically associate with the B cell ant... | KEEP AS NON CORE | Summary: Co-precipitation of native CD20 with tagged or truncated CD20 indicated homo-tetramer formation. Reason: Homo-oligomerization is well supported, though cryo-EM structures resolve CD20 as a dimer (PMID:32079680), so the tetrameric stoichiometry in native membranes remains uncertain. Not the core function. Supporting Evidence: PMID:18474602 we provide here direct evidence of CD20 homo-oligomerization into tetramers PMID:32079680 revealing CD20 as a compact double-barrel dimer bound by two RTX antigen-binding fragments (Fabs) |
| GO:0051262 protein tetramerization | IDA PMID:7684739 Transfection of the CD20 cell surface molecule into ectopic ... | KEEP AS NON CORE | Summary: Cross-linking/immunoprecipitation suggested CD20 is present as a multimeric oligomer. Reason: The cited data show multimeric oligomers rather than a defined tetramer; later structural work shows a dimeric unit. Retained as non-core, deferring to the curator who read the full text. Supporting Evidence: PMID:7684739 Biochemical cross-linking of cell-surface molecules with subsequent immunoprecipitation analysis of CD20 suggests that CD20 may be present as a multimeric oligomer within the membrane PMID:32079680 revealing CD20 as a compact double-barrel dimer bound by two RTX antigen-binding fragments (Fabs) |
| GO:0070062 extracellular exosome | HDA PMID:20458337 MHC class II-associated proteins in B-cell exosomes and pote... | KEEP AS NON CORE | Summary: Identified in the proteome of B cell-derived exosomes. Reason: CD20 is a plasma membrane protein that is carried on B-cell exosome membranes; real but not a site where CD20 performs its function. Supporting Evidence: PMID:20458337 we first analyzed the total proteome of highly purified B cell-derived exosomes using sensitive and accurate mass spectrometry (MS), and identified 539 proteins PMID:20458337 These include HSC71, HSP90, 14-3-3Ι, CD20 and pyruvate kinase type M2 (PKM2) |
| GO:1902656 calcium ion import into cytosol | IDA PMID:7684739 Transfection of the CD20 cell surface molecule into ectopic ... | ACCEPT | Summary: Expression of CD20 in lymphoid and non-lymphoid cells increased transmembrane Ca2+ conductance, and anti-CD20 antibody enhanced this conductance. Reason: Direct electrophysiological evidence that CD20 mediates/regulates calcium entry from the extracellular space into the cytosol; consistent with later SOC entry work. Supporting Evidence: PMID:7684739 Transfection of human T and mouse pre-B lymphoblastoid cell lines with CD20 cDNA and subsequent stable expression of CD20 specifically increased transmembrane Ca2+ conductance. PMID:7684739 these findings indicate that CD20 directly regulates transmembrane Ca2+ conductance in B lymphocytes |
| GO:1905665 positive regulation of calcium ion import across plasma membrane | IEA GO_REF:0000107 | ACCEPT | Summary: Electronic ortholog transfer from mouse of positive regulation of calcium ion import across plasma membrane. Reason: Consistent with mouse knockout (reduced CD19-induced Ca2+ responses) and human data showing CD20 promotes BCR-stimulated calcium influx; the regulatory framing is appropriate given uncertainty whether CD20 is itself the channel. Supporting Evidence: PMID:14688067 CD19-induced intracellular calcium responses were significantly reduced in CD20(-/-) B cells, with a less dramatic effect on IgM-induced responses. PMID:12920111 B cell receptor-stimulated influx was significantly reduced by downregulation of CD20 expression using short interfering RNA and also by cholesterol depletion |
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Download this section (compressed HTML)Q: Does CD20 conduct Ca2+ directly as an oligomeric channel, or does it couple the BCR to ORAI/STIM store-operated channels?
Q: What is the native oligomeric state of CD20 in resting B cell membranes (dimer as in cryo-EM vs tetramer by co-IP), and does BCR engagement change it?
Q: Why is CD20 loss selectively deleterious for T cell-independent antibody responses while T-dependent responses and B cell development are largely normal?
Experiment: Reconstitute purified human CD20 in liposomes/planar lipid bilayers and measure Ca2+ and Sr2+ permeation, with and without rituximab.
Hypothesis: CD20 oligomers form an intrinsic cation-permeable pore.
Type: electrophysiology/reconstitution
Experiment: Knock out ORAI1/STIM1 in human B cell lines and test whether CD20 overexpression still enhances BCR-triggered store-operated calcium entry.
Hypothesis: CD20 acts upstream of or as a regulator of ORAI/STIM SOC channels rather than as an independent channel.
Type: genetic epistasis/calcium imaging
Experiment: Super-resolution imaging and proximity labeling of endogenous CD20, IgM-BCR, IgD-BCR and CD19 in resting versus activated primary human B cells.
Hypothesis: CD20 organizes BCR nanoclusters in resting B cells and is released upon receptor engagement.
Type: imaging/proteomics
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